A 45-year-old man with chronic kidney disease requires an urgent blood transfusion. He has received multiple transfusions over the past 5 years. A transfusion reaction occurs 30 minutes after the start of infusion, characterized by fever, chills, and mild dyspnea. What is the most common cause of acute transfusion reactions in multiply transfused patients?

Explanation

## Acute Transfusion Reactions: Epidemiology and Classification **Key Point:** Febrile non-haemolytic transfusion reaction (FNHTR) is the most common acute transfusion reaction overall, occurring in 0.5–1% of transfusions, and is especially frequent in multiply transfused patients due to alloimmunization to HLA and granulocyte antigens. ### Comparative Incidence and Features | Reaction Type | Incidence | Onset | Mechanism | Severity | |---------------|-----------|-------|-----------|----------| | **FNHTR** | 0.5–1% (most common) | 30 min–2 hrs | HLA/granulocyte alloimmunization | Mild–moderate | | Acute haemolytic | 1 in 10,000–100,000 | Minutes | ABO/Rh incompatibility | Severe | | Anaphylactic | 1 in 20,000–50,000 | Seconds–minutes | IgE-mediated (IgA deficiency) | Severe | | TRALI | 1 in 5,000 | 1–6 hrs | HLA/HNA antibodies (donor) | Severe | ### Why FNHTR in Multiply Transfused Patients? 1. **Cumulative HLA alloimmunization**: Multiple transfusions expose the patient to donor HLA antigens on white blood cells and platelets 2. **Granulocyte-specific antibodies**: Develop after repeated exposure 3. **Immune complex formation**: Leads to cytokine release (TNF-α, IL-1, IL-6) 4. **Fever and chills**: Result from pyrogenic cytokines, not haemolysis **High-Yield:** The clinical triad of **fever + chills + mild dyspnea** in a multiply transfused patient is classic for FNHTR. Absence of haemoglobinuria, hyperbilirubinaemia, and haemolytic markers confirms non-haemolytic nature. **Clinical Pearl:** FNHTR is preventable by **pre-transfusion leukoreduction** (removes WBCs and platelets carrying HLA antigens) or pre-medication with antipyretics and antihistamines. **Mnemonic: "FNHTR = Fever, No Haemolysis, Transfused Repeatedly"** — the patient's history of multiple transfusions is the key epidemiological clue. ### Differential Diagnosis at Bedside ```mermaid flowchart TD A[Acute Transfusion Reaction]:::outcome --> B{Timing?}:::decision B -->|Seconds-minutes| C[Anaphylaxis or acute haemolytic]:::urgent B -->|30 min-2 hours| D{Haemolysis markers?}:::decision D -->|Yes: haemoglobinuria, ↑ bilirubin| E[Acute haemolytic reaction]:::urgent D -->|No: fever, chills only| F[FNHTR - most common]:::action B -->|1-6 hours| G{Respiratory distress?}:::decision G -->|Yes| H[TRALI]:::urgent G -->|No| F ``` [cite:Harrison 21e Ch 406] [cite:Robbins 10e Ch 4]